Autoimmune regulator (AIRE) gene on chromosome 21: Implications for autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) and more common manifestations of endocrine autoimmunity

Abstract

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is a rare, but well-defined monogenic disorder that is caused by mutations in the autoimmune regulator (AIRE) gene on chromosome 21q22.3. Patients most often suffer from loss of endocrine function in the parathyroid and adrenal glands but may also develop Type 1 diabetes, thyroid disease or hypogonadism. The disease may therefore serve as a model for sporadic endocrine autoimmunity and help to develop new screening and prevention methods. To date at least 46 mutations of AIRE have been identified in affected individuals. Little is known about heterozygosity states but patients with the more prevalent isolated autoimmune endocrinopathies such as Type 1 diabetes, Hashimoto’s thyroiditis, Graves’ or Addison’s disease do not have any of the common mutations. This does not rule out AIRE to be affected either by so far unknown or regulatory variants. The recent characterization of AIRE knockout mice with similar immune pathological findings compared to the human setting will help to elucidate endocrine autoimmunity.